Cerebrovascular Disease Detected on Preprocedural Computed Tomography in Patients With Severe Aortic Stenosis Undergoing Aortic Valve Replacement.

BACKGROUND: There is a scarcity of data on the prevalence and clinical impact of cerebrovascular disease detected on preprocedural computed tomography (CT) before aortic valve replacement (AVR) in patients with severe aortic stenosis. METHODS AND RESULTS: Among patients with severe aortic stenosis undergoing AVR, the authors compared clinical outcomes between patients with and without cerebrovascular disease detected on preprocedural CT, which was defined as chronic brain infarction or hemorrhage. The primary outcome measure in this study was a composite of all-cause death or stroke. Among 567 study patients, 200 patients (35.3%) had cerebrovascular disease on preprocedural CT. Among 200 patients with cerebrovascular disease on preprocedural CT, only 28.5% of patients had a clinical history of symptomatic stroke. The cumulative 3-year incidence of death or stroke was higher in patients with cerebrovascular disease on preprocedural CT than in those without cerebrovascular disease on preprocedural CT (40.7% versus 24.1%, log-rank P<0.001). After adjusting for confounders, the higher risk of patients with cerebrovascular disease on preprocedural CT relative to those without remained significant for death or stroke (hazard ratio [HR], 1.42 [95% CI, 1.02-1.98]; P=0.04). Among 200 patients with cerebrovascular disease on preprocedural CT, patients with prior symptomatic stroke compared with those without were not associated with higher adjusted risk for death or stroke (HR, 1.18 [95% CI, 0.72-1.94]; P=0.52). CONCLUSIONS: Among patients with severe aortic stenosis undergoing AVR, a substantial proportion had cerebrovascular disease on preprocedural CT, with a clinical history of symptomatic stroke in one-fourth of patients. Regardless of history of symptomatic stroke, patients with cerebrovascular disease on preprocedural CT had worse clinical outcomes compared with those without cerebrovascular disease on preprocedural CT.

Living-donor lobar lung transplantation for pulmonary Langerhans cell histiocytosis complicated by extensive thrombi in central pulmonary arteries.

BACKGROUND: Pulmonary Langerhans cell histiocytosis (PLCH) is a rare disorder characterized by the proliferation of Langerhans cells along the small airways, which causes nodular and cystic changes in the lung parenchyma. Lung transplantation can be a life-saving option for patients with severe respiratory failure or pulmonary hypertension. Herein, we present a case of successful lung transplantation in a patient with PLCH who developed unusually large thrombi in the central pulmonary artery. CASE PRESENTATION: A 47-year-old woman with 16-year history of PLCH with rapidly developing respiratory failure was admitted to our hospital for the evaluation of a lung transplant. Enhanced computed tomography revealed large thrombi in dilated central pulmonary arteries. Right heart catheterization revealed severe pulmonary hypertension, with a mean pulmonary artery pressure of 48 mmHg. The thrombi shrank markedly after 3 months of anticoagulation therapy. However, the respiratory status of the patient did not improve. We performed bilateral living-donor lobar lung transplantation with thrombectomy under extracorporeal membrane oxygenation for the remaining thrombi in the main pulmonary arteries. The dilated main pulmonary arteries of the recipient required direct plication for size mismatch. The patient survived in good condition for more than 2 years with no recurrence of thrombosis. CONCLUSION: Preoperative anticoagulation therapy for massive thrombi in the pulmonary arteries was effective and led to safe lung transplantation.

Clinical effects of direct oral anticoagulants in elderly patients with a bioprosthetic valve and atrial fibrillation.

BACKGROUND: Current guidelines recommend direct oral anticoagulants (DOACs) and warfarin for patients with atrial fibrillation (AF) who have a bioprosthetic valve (BPV). However, the data related to elderly patients (aged ≥80 years) with BPV replacement and AF are limited. METHODS: This post-hoc subgroup analysis of a BPV-AF Registry enrolled 752 patients with BPV replacement and AF. The primary net outcome was a composite of cardiac death, stroke, systemic embolism, major bleeding, and cardiovascular events. RESULTS: Among 752 patients, 429 (57%) patients were ≥ 80 and 323 (43%) were < 80 years old. The higher risk in patients aged ≥80 than <80 years was significant for the net outcome (hazard ratio [HR], 2.04; 95% confidence interval [CI], 1.31-3.17; P = 0.001). After adjustment for confounders, there was no statistically significant difference between warfarin (reference) and DOAC users in the risk of net outcomes (adjusted HR, 1.26; 95% CI, 0.71-2.24; P = 0.44), stroke and systemic embolism (adjusted HR, 2.01; 95% CI, 0.48-8.38; P = 0.34), and major bleeding (adjusted HR, 0.73; 95% CI, 0.11-4.98; P = 0.75) in patients aged ≥80 years old as well as those aged <80 years. Among 489 warfarin users, the cumulative incidence of net outcomes tended to be higher in patients aged ≥80 than <80 years (12.2% vs. 5.7% at 1 year, log-rank P = 0.002). Among 263 DOAC users, however, it was similar between patients aged ≥80 and < 80 years. CONCLUSIONS: The present study demonstrated that DOAC showed similar efficacy and safety compared with warfarin even in elderly patients aged ≥80 years with BPV replacement and AF.

miR-124-3p downregulates EGR1 to suppress ischemia-hypoxia reperfusion injury in human iPS cell-derived cardiomyocytes.

Ischemic heart diseases are a major global cause of death, and despite timely revascularization, heart failure due to ischemia-hypoxia reperfusion (IH/R) injury remains a concern. The study focused on the role of Early Growth Response 1 (EGR1) in IH/R-induced apoptosis in human cardiomyocytes (CMs). Human induced pluripotent stem cell (hiPSC)-derived CMs were cultured under IH/R conditions, revealing higher EGR1 expression in the IH/R group through quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting (WB). Immunofluorescence analysis (IFA) showed an increased ratio of cleaved Caspase-3-positive apoptotic cells in the IH/R group. Using siRNA for EGR1 successfully downregulated EGR1, suppressing cleaved Caspase-3-positive apoptotic cell ratio. Bioinformatic analysis indicated that EGR1 is a plausible target of miR-124-3p under IH/R conditions. The miR-124-3p mimic, predicted to antagonize EGR1 mRNA, downregulated EGR1 under IH/R conditions in qRT-PCR and WB, as confirmed by IFA. The suppression of EGR1 by the miR-124-3p mimic subsequently reduced CM apoptosis. The study suggests that treatment with miR-124-3p targeting EGR1 could be a potential novel therapeutic approach for cardioprotection in ischemic heart diseases in the future.

Mycotic pulmonary artery pseudoaneurysm following total arch replacement: a case report.

BACKGROUND: Although the true prevalence and incidence are not clearly known, mycotic pulmonary artery aneurysm is a potentially devastating condition that leads to high mortality, over 60% if untreated. Among them, mycotic pulmonary artery pseudoaneurysm, which occurs in relatively central areas, has rarely been reported. We report an extremely rare case of a late complication with a mycotic pulmonary artery pseudoaneurysm, presumably due to infective endocarditis, in a 68-year-old woman 4 months after total arch replacement. CASE PRESENTATION: A 68-year-old woman was referred to our department for 2 weeks with fever of unknown origin. She had a history of emergency total arch replacement for an acute type A aortic dissection 4 months earlier and chronic rheumatoid arthritis on monthly subcutaneous tocilizumab treatment for several years. Blood culture was positive for Enterococcus faecalis. Transthoracic and transesophageal echocardiography revealed a left ventricular ejection fraction of 58%, severe mitral regurgitation with a 15-mm diameter vegetation on the anterior mitral leaflet, and severe aortic insufficiency with string-like structures. Contrast computed tomography showed a focal saccular outpouching from the right pulmonary artery. On 18F-fluorodeoxyglucose (FDG) positron emission tomography, focal uptake of FDGs was observed along the same lesion of the pulmonary artery and ascending-arch graft. The patient eventually recovered after the surgical intervention of mitral and aortic valve replacement, re-total arch replacement, pulmonary artery repair, application of omental flap, and antibiotics without any evidence of re-infection after 1 year. CONCLUSIONS: We report a successful surgical repair of mycotic pulmonary artery pseudoaneurysm 4 months after total arch replacement for acute type A aortic dissection. This report describes an effective treatment for an extremely rare postoperative condition.

Clinically significant incidental noncardiac findings on preprocedural computed tomography in patients with aortic stenosis undergoing aortic-valve replacement.

BACKGROUND: There is a scarcity of data on the prevalence of abnormal findings on preprocedural computed tomography (CT) before aortic valve replacement (AVR) in patients with aortic stenosis (AS). METHODS: Among consecutive 593 patients with severe AS who were planned to undergo AVR, we evaluated the prevalence of clinically significant incidental noncardiac findings on preprocedural CT. Clinically significant incidental noncardiac findings were defined as newly detected abnormalities that required therapy, consultation for expert, further investigation, or clinical follow-up. RESULTS: The mean age was 82.0 years and 39.5 % of the patients were men. Of those, 78.4 % of the patients were treated with transcatheter aortic valve implantation (TAVI) and 21.6 % of the patients were treated with surgical AVR (SAVR). There were 271 clinically significant incidental noncardiac findings in 227 patients (38.3 %) including 2.5 % of malignancy. The prevalence of clinically significant incidental noncardiac findings were higher in the TAVI group than in the SAVR group (40.2 % versus 31.3 %). The prevalence of clinically significant incidental noncardiac findings were lower in patients under 60 years of age (10.0 %) than in patients over 60 years of age (60-69 years: 40.0 %, 70-79 years: 34.3 %, 80-89 years: 39.7 %, and ≥90 years: 42.1 %). CONCLUSIONS: Clinically significant incidental noncardiac findings were newly identified on preprocedural CT in approximately 40 % of patients with severe AS undergoing AVR including 2.5 % of malignancy.

Concomitant Mitral Regurgitation in Severe Aortic Stenosis　- Insights From the CURRENT AS Registry-2.

BACKGROUND: Data on concomitant mitral regurgitation (MR) in patients with severe aortic stenosis (AS) are scarce.Methods and Results: We investigated the risk of concomitant MR in patients with severe AS in the CURRENT AS Registry-2 according to initial treatment strategy (transcatheter aortic valve implantation [TAVI], surgical aortic valve replacement [SAVR], or conservative). Among 3,365 patients with severe AS, 384 (11.4%) had moderate/severe MR (TAVI: n=126/1,148; SAVR: n=68/591; conservative: n=190/1,626). The cumulative 3-year incidence for death or heart failure (HF) hospitalization was significantly higher in the moderate/severe than no/mild MR group in the entire population (54.6% vs. 34.3%, respectively; P<0.001) and for each treatment strategy (TAVI: 45.0% vs. 31.8% [P=0.006]; SAVR: 31.9% vs. 18.7% [P<0.001]; conservative: 67.8% vs. 41.6% [P<0.001]). The higher adjusted risk of moderate/severe MR relative to no/mild MR for death or HF hospitalization was not significant in the entire population (hazard ratio [HR] 1.15; 95% confidence interval [CI] 0.95-1.39; P=0.15); however, the risk was significant in the SAVR (HR 1.92; 95% CI 1.04-3.56; P=0.04) and conservative (HR 1.30; 95% CI 1.02-1.67; P=0.04) groups, but not in the TAVI group (HR 1.03; 95% CI 0.70-1.52; P=0.86), despite no significant interaction (Pinteraction=0.37). CONCLUSIONS: Moderate/severe MR was associated with a higher risk for death or HF hospitalization in the initial SAVR and conservative strategies, while the association was less pronounced in the initial TAVI strategy.

Surgical treatment for a child with traumatic ventricular septal rupture and ventricular aneurysm.

A five-year-old boy was diagnosed with the ventricular septal rupture and ventricular aneurysm after blunt chest trauma in child abuse. Because of the intractable heart failure, he underwent operation in subacute period. Postoperative course was uneventful. The blunt cardiac injury in children can be caused by mild trauma and can be lethal. Surgical intervention should be considered when the clinical condition is unstable.

Two cases of pararenal artery aortic aneurysm treatment after pancreaticoduodenectomy and abdominal aortic aneurysm stent grafting.

BACKGROUND: Acute pancreatitis caused by surgical procedures may occur less frequently in surgeries for aortic aneurysm involving the abdominal branch. However, in such cases, the associated mortality rate increases significantly. There have been few reports on abdominal aortic aneurysm surgery after pancreatoduodenectomy; as such the incidence of postoperative pancreatitis remains unclear. CASE PRESENTATION: Two cases of pararenal artery aortic aneurysm after pancreaticoduodenectomy and endovascular aneurysm repair (EVAR) for an abdominal aortic aneurysm are reported. In the first case, a 74-year-old man was diagnosed with abdominal aortic aneurysm and duodenal cancer 6 years earlier and underwent pancreaticoduodenectomy after EVAR. Subsequently, the abdominal aorta expanded to 58 mm at the level of the renal artery proximal to the EVAR site. Graft replacement was performed through a left thoraco-retroperitoneal incision. However, the patient died from acute pancreatitis, believed to be caused by intraoperative manipulation. Given this initial experience, in the second case, a 77-year-old man had undergone a pancreaticoduodenectomy for a gastrointestinal stromal tumor 17 years earlier and EVAR for an abdominal aortic aneurysm 10 years earlier. The abdominal aorta had expanded to 50 mm immediately below the right renal artery on the proximal side of the EVAR. Subsequently, hematuria was noted, and he was diagnosed with right ureteral cancer. Autologous transplantation of the left kidney and EVAR was performed avoiding manipulation of the area around the pancreas and achieved good results. Combined right renal and ureteral resections were performed 20 days after EVAR. CONCLUSIONS: While performing aortic surgery after pancreaticoduodenectomy, surgeons should avoid manipulating tissues around the pancreas.

Transarterial Embolization of Type 2 Endoleak Post Thoracic Endovascular Aortic Repair (TEVAR) Using a Triaxial System With a 1.3-F Microcatheter: A Case Report.

Although transarterial embolization is recognized as a treatment for type 2 endoleaks, it can occasionally be challenging. We report the case of an 86-year-old man who presented with an enlarging thoracoabdominal aortic aneurysm following thoracic endovascular aortic repair. Using a triaxial system with a 1.3-F microcatheter, transarterial embolization of a type 2 endoleak was successfully performed through a long and tortuous arterial route comprising the thoracodorsal and ninth intercostal arteries. The postoperative clinical course was uneventful, and computed tomography obtained six days later showed no endoleak in the thoracoabdominal aortic aneurysm. This case suggests the usefulness of a triaxial system with a 1.3-F microcatheter for transarterial embolization of type 2 endoleaks.

Modeling mutation-specific arrhythmogenic phenotypes in isogenic human iPSC-derived cardiac tissues.

Disease modeling using human induced pluripotent stem cells (hiPSCs) from patients with genetic disease is a powerful approach for dissecting pathophysiology and drug discovery. Nevertheless, isogenic controls are required to precisely compare phenotypic outcomes from presumed causative mutations rather than differences in genetic backgrounds. Moreover, 2D cellular models often fail to exhibit authentic disease phenotypes resulting in poor validation in vitro. Here we show that a combination of precision gene editing and bioengineered 3D tissue models can establish advanced isogenic hiPSC-derived cardiac disease models, overcoming these drawbacks. To model inherited cardiac arrhythmias we selected representative N588D and N588K missense mutations affecting the same codon in the hERG potassium channel gene KCNH2, which are reported to cause long (LQTS) and short (SQTS) QT syndromes, respectively. We generated compound heterozygous variants in normal hiPSCs, and differentiated cardiomyocytes (CMs) and mesenchymal cells (MCs) to form 3D cardiac tissue sheets (CTSs). In hiPSC-derived CM monolayers and 3D CTSs, electrophysiological analysis with multielectrode arrays showed prolonged and shortened repolarization, respectively, compared to the isogenic controls. When pharmacologically inhibiting the hERG channels, mutant 3D CTSs were differentially susceptible to arrhythmic events than the isogenic controls. Thus, this strategy offers advanced disease models that can reproduce clinically relevant phenotypes and provide solid validation of gene mutations in vitro.

18F-FDG PET/CT in left atrial undifferentiated pleomorphic sarcoma with osteosarcomatous differentiation.

Primary cardiac sarcomas are rare and sometimes difficult to discern from benign tumors and intracardiac thrombi. We describe the ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/CT findings in a case of left atrial undifferentiated pleomorphic sarcoma with osteosarcomatous differentiation, presenting with severe mitral regurgitation and pulmonary hypertension. The tumor presented as a broad-base mass protruding into the cardiac lumen, accompanied by punctate calcification-like high attenuation on CT. 18F-FDG PET/CT revealed high 18F-FDG uptake in the mass. Severe mitral regurgitation, a rare manifestation, was caused by tumor extension to the mitral valve leaflets and subvalvular tissue, which was best visualized on transesophageal echocardiography. This case illustrates the importance of multimodal diagnostic approaches including 18F-FDG PET/CT, which can facilitate accurate diagnosis and timely initiation of curative treatment, ultimately saving the patient's life. Learning objective: Firstly, cardiac sarcomas, particularly those with calcification/ossification, are rare and may mimic benign tumors and chronic intracardiac thrombi. Multimodal imaging approach, including 18F-FDG PET/CT, may be helpful in the accurate diagnosis of malignancies. Second, left atrial undifferentiated pleomorphic sarcoma has the potential to extensively spread along the endocardium and can extend to involve the valve leaflets, resulting in mitral regurgitation and pulmonary hypertension.

Pleurodesis using OK-432 for persistent pleural effusion after cardiac surgery in the neonatal period or early infancy.

OBJECTIVE: To evaluate the efficacy of pleurodesis using OK-432 after cardiac surgery in the neonatal period or early infancy. METHODS: We retrospectively reviewed the data of 11 consecutive patients who underwent cardiac surgery in the neonatal period or early infancy and pleurodesis using OK-432 for persistent postoperative pleural effusion in two institutions. RESULTS: The median age at surgery was 8 days (interquartile range [IR], 2-18) with a body weight of 2.84 kg (IR, 2.30-3.07). The maximum amount of pleural drainage before pleurodesis was 94.7 (IR, 60.2-107.7) ml/kg/day. Pleurodesis was initiated at postoperative day 20 (IR, 17-22) and performed in bilateral pleural spaces in seven patients and unilateral in four. The median numbers of injection were 4 (IR, 3-6) times per patient and 3 (IR, 2-3) times per pleural space. In 10 patients, pleural effusion was decreased effectively, and drainage tubes were removed without reaccumulation within 15 (IR, 12-28) days after initial pleurodesis. However, in one patient, with severe lymphedema, pleural effusion was uncontrollable, resulting in death due to sepsis. Adverse events were observed in nine patients; temporal deterioration of lung compliance and arterial blood gas occurred in two, insufficient drainage requiring new chest tube(s) in five, temporal atrial tachyarrhythmia in one, and lymphedema in four. CONCLUSIONS: Pleurodesis using OK-432 is effective and reliable for persistent postoperative pleural effusion in neonates and early infants. Most of the complications, which derived from inflammatory reactions, were temporary and controllable. However, severe lymphedema is difficult to control.

In-hospital outcomes after SAVR or TAVI in patients with severe aortic stenosis.

There were no data comparing the in-hospital outcomes after transcatheter aortic valve implantation (TAVI) with those after surgical aortic valve replacement (SAVR) in Japan. Among consecutive patients with severe AS between April 2018 and December 2020 in the CURRENT AS Registry-2, we identified 1714 patients who underwent aortic valve replacement (TAVI group: 1134 patients, and SAVR group: 580 patients). Patients in the TAVI group were much older (84.4 versus 73.6 years, P < 0.001) and more often had comorbidities than those in the SAVR group. In-hospital death rate was numerically lower in the TAVI group than in the SAVR group (0.6% versus 2.2%). After excluding patients with dialysis, in-hospital death rate was very low and comparable in the TAVI and SAVR groups (0.6% versus 0.8%). The rates of major bleeding and new-onset atrial fibrillation during index hospitalization were higher after SAVR than after TAVI (72% versus 20%, and 26% versus 4.6%, respectively), while the rate of pacemaker implantation was higher after TAVI than after SAVR (8.1% versus 2.4%). Regarding the echocardiographic data at discharge, the prevalence of patient-prosthesis mismatch was lower in the TAVI group than in the SAVR group (moderate: 9.0% versus 26%, and severe: 2.6% versus 4.8%). In this real-world data in Japan, TAVI compared with SAVR was chosen in much older patients with more comorbidities with severe AS. In-hospital death rate was numerically lower in the TAVI group than in the SAVR group.

Minimal access aortic surgery.

Recently, there have been significant advances in small incisions through right thoracic cavity including robotic surgery. We have been performing aortic surgery through a partial sternotomy for ascending, arch, and aortic root replacement. In this article, we would like to provide tips for small incision aortic surgery at our institution by showing surgical videos of two cases. Supplementary Information: The online version contains supplementary material available at 10.1007/s12055-023-01578-5.